The long-term goal of this study is to understand the involvement of different types of inhibitory neocortical interneurons in the processing of sensory inputs in the mammalian neocortex. Inhibitory interneurons exert a profound influence on signal processing in the somatosensory system and have been shown to influence the postnatal critical period of sensory plasticity. The short-term overall goal of this proposal is to test the hypothesis that developmental changes in the synaptic properties of thalamocortical inputs onto neocortical interneurons and in the intrinsic properties of neocortical interneurons, which receive direct thalamic input, are responsible for the enhancement of inhibition produced by thalamic stimulation in older animals. Patch-clamp recordings of interneurons in thalamocortical slices, single-cell RT-PCR, and Neurolucida reconstructions will be used to address the following Specific Aims. (1) Neocortical interneurons (1-18 days postnatal), which are excited by thalamocortical afferents, will be examined for developmental changes in their intrinsic membrane properties that would make them more susceptible to excitation by thalamocortical afferents. The subtypes of neocortical interneurons excited by thalamic input will also be determined. (2) The morphology of the interneurons receiving direct thalamic input will be examined for developmental changes and to determine whether excited interneurons exhibit axonal and dendritic arbors that extend between barrels. (3) Thalamocortical synapses onto neocortical interneurons will be examined for developmental changes in the electrophysiological properties of the monosynaptic responses, the ratio of NMDA receptor currents to AMPA receptor currents, and the Ca2+-permeability of AMPA receptors. This research will advance our understanding of how inhibitory circuits are developmentally regulated in terms of synaptic changes and morphological changes. A better understanding of the development of cortical inhibition is likely to have relevance to the understanding of various cerebral epilepsies in which there is an imbalance between excitation and inhibition.